BioEd Online

When the chikungunya virus hit the French Caribbean territories of Martinique and Guadeloupe in a 2013–15 epidemic, around half of the population fell ill. Few people died from the disease, which causes high fever and severe joint pain. But years after the infection, many of those affected still struggle to dress themselves, to grip objects and to close their fists, says Fabrice Simon, a chikungunya researcher at Laveran military teaching hospital in Marseille, France.

Advocates are attempting to accelerate the development of a vaccine for this disabling disease, which is endemic in the tropics and sub-tropics — regions that are home to some 1.3 billion people. Epidemiologists, vaccine developers and regulators are meeting in New Delhi on 5–6 February to review the latest data on vaccine candidates, and to consider how to get the promising ones to market.

“The timing is right; there are promising vaccine candidates in the pipeline; what’s needed now is momentum,” says Johan Holst, a vaccine specialist at the Coalition for Epidemic Preparedness Innovations (CEPI) in Oslo, an influential body formally launched in 2017 to speed up the development of vaccines against epidemic threats. Its members include the Bill & Melinda Gates Foundation, the Wellcome Trust, the World Economic Forum, the European Commission and several governments, including those of Germany and Japan.

Some 16 vaccine candidates are in preclinical studies in animals, 5 are in phase 1 clinical trials, and 2 are in phase 2 clinical trials, according to an ongoing CEPI survey. One of the furthest developed candidates is produced by Themis Bioscience, a vaccine maker in Vienna. It has tweaked an existing measles vaccine to produce chikungunya virus proteins in human cells and so elicit an immune response. The firm has begun phase 2 trials to test the vaccine's safety in several hundred volunteers at sites in Austria, Germany and Puerto Rico. Katrin Ramsauer, head of clinical development at Themis, says that she will share some interim findings at the workshop, including that the vaccine elicited high levels of antibodies against the chikungunya virus.

Lifelong protection

Making an effective vaccine against chikungunya could be relatively easy, according to many vaccine scientists, because natural infection with the disease provides lifelong immunity to the virus. The bigger challenges revolve around the epidemiology of chikungunya — although the disease is now endemic across vast swathes of the world, its epidemic nature makes it difficult to do the phase 3 trials that are the final step towards getting a vaccine licensed by regulators. These involve enrolling thousands of volunteers in areas where there is a risk of infection. “Nobody knows where the next outbreaks will be,” says Ramsauer.

Some scientists argue that regulators, such as the US Food and Drug Administration (FDA), could issue a provisional licence for a chikungunya vaccine without first requiring evidence from phase 3 trials. They point to the FDA’s accelerated approval programme, under which drugs that treat serious conditions and which fill an unmet medical need can be approved early on the basis of other kinds of evidence that a vaccine will probably work in humans.

In the case of chikungunya, for instance, researchers could take human antibodies against the disease from people who had been vaccinated in phase 1 and 2 trials, and transfer them to non-human primates, suggests Scott Weaver, who studies mosquito-borne diseases and vaccines for chikungunya at the University of Texas Medical Branch in Galveston.

If this protected the primates against chikungunya in experiments, that would provide strong surrogate evidence that the vaccine could work in humans. Given a provisional licence, researchers could then estimate the vaccine’s true effectiveness during its use in outbreaks, Weaver says.

Themis is holding discussions with both the FDA and the European Medicines Agency. “We do appreciate that both agencies are well aware of the medical burden of chikungunya disease, and are also aware of the practical issues a manufacturer needs to overcome,” Ramsauer says.